Department of Biomedical Sciences, University of Padova, Padova, Italy.
Department of Medicine and Surgery, University of Parma, Parma, Italy.
J Cachexia Sarcopenia Muscle. 2023 Apr;14(2):794-804. doi: 10.1002/jcsm.13173. Epub 2023 Jan 28.
Ageing is accompanied by a progressive loss of skeletal muscle mass and strength, potentially determining the insurgence of sarcopenia. Evidence suggests that motoneuron and neuromuscular junction (NMJ) degeneration contribute to sarcopenia pathogenesis. Seeking for strategies able to slow down sarcopenia insurgence and progression, we investigated whether a 2-year mixed-model training involving aerobic, strength and balance exercises would be effective for improving or preserving motoneuronal health and NMJ stability, together with muscle mass, strength and functionality in an old, sarcopenic population.
Forty-five sarcopenic elderly (34 females; 11 males) with low dual-energy X-ray absorptiometry (DXA) lean mass and Short Physical Performance Battery (SPPB) score <9 were randomly assigned to either a control group [Healthy Aging Lifestyle Education (HALE), n = 21] or an intervention group [MultiComponent Intervention (MCI), n = 24]. MCI trained three times per week for 2 years with a mix of aerobic, strength and balance exercises matched with nutritional advice. Before and after the intervention, ultrasound scans of the vastus lateralis (VL), SPPB and a blood sample were obtained. VL architecture [pennation angle (PA) and fascicle length (Lf)] and cross-sectional area (CSA) were measured. As biomarkers of neuronal health and NMJ stability status, neurofilament light chain (NfL) and C-terminal agrin fragment (CAF) concentrations were measured in serum. Differences in ultrasound parameters, NfL and CAF concentration and physical performance between baseline and follow-up were tested with mixed ANOVA or Wilcoxon test. The relationship between changes in physical performance and NfL or CAF concentration was assessed through correlation analyses.
At follow-up, MCI showed preserved VL architecture (PA, Lf) despite a reduced CSA (-8.4%, P < 0.001), accompanied by maintained CAF concentration and ameliorated overall SPPB performance (P = 0.007). Conversely, HALE showed 12.7% decrease in muscle CSA (P < 0.001), together with 5.1% and 5.5% reduction in PA and Lf (P < 0.001 and P = 0.001, respectively), and a 6.2% increase in CAF (P = 0.009) but improved SPPB balance score (P = 0.007). NfL concentration did not change in either group. In the population, negative correlations between changes in CAF concentration and SPPB total score were found (P = 0.047), whereas no correlation between NfL and SPPB variations was observed.
The present findings suggest that our 2-year mixed aerobic, strength and balance training seemed effective for preventing the age and sarcopenia-related increases in CAF concentration, preserving NMJ stability as well as muscle structure (PA and Lf) and improving physical performance in sarcopenic older individuals.
衰老伴随着骨骼肌质量和力量的逐渐丧失,这可能导致肌肉减少症的发生。有证据表明,运动神经元和神经肌肉接头(NMJ)的退化有助于肌肉减少症的发病机制。为了寻找能够减缓肌肉减少症发生和进展的策略,我们研究了为期 2 年的混合模式训练,包括有氧运动、力量和平衡训练,是否能有效改善或维持老年、肌肉减少症患者的运动神经元健康和 NMJ 稳定性,以及肌肉质量、力量和功能。
45 名患有肌肉减少症的老年人(34 名女性;11 名男性),双能 X 线吸收法(DXA)测定的瘦体重低,短体物理性能电池(SPPB)评分<9,随机分为对照组[健康老龄化生活方式教育(HALE),n=21]或干预组[多成分干预(MCI),n=24]。MCI 每周训练 3 次,持续 2 年,混合有氧运动、力量和平衡训练,并辅以营养建议。干预前后,对股外侧肌(VL)、SPPB 和血样进行超声扫描。测量 VL 结构[羽毛角(PA)和束长(Lf)]和横截面积(CSA)。作为神经元健康和 NMJ 稳定性状态的生物标志物,血清中神经丝轻链(NfL)和 C 端神经胶质纤维酸性蛋白片段(CAF)的浓度。采用混合方差分析或 Wilcoxon 检验比较基线和随访时超声参数、NfL 和 CAF 浓度及身体表现的差异。通过相关分析评估身体表现变化与 NfL 或 CAF 浓度之间的关系。
随访时,MCI 组 VL 结构(PA、Lf)保持不变,尽管 CSA 减少了(-8.4%,P<0.001),同时 CAF 浓度保持不变,整体 SPPB 表现得到改善(P=0.007)。相反,HALE 组肌肉 CSA 减少了 12.7%(P<0.001),PA 和 Lf 分别减少了 5.1%和 5.5%(P<0.001 和 P=0.001),CAF 增加了 6.2%(P=0.009),但 SPPB 平衡评分提高(P=0.007)。两组的 NfL 浓度均无变化。在该人群中,发现 CAF 浓度变化与 SPPB 总分之间存在负相关(P=0.047),而 NfL 与 SPPB 变化之间无相关性。
本研究结果表明,我们为期 2 年的混合有氧、力量和平衡训练似乎有效,可预防衰老和肌肉减少症相关的 CAF 浓度升高,维持 NMJ 稳定性以及肌肉结构(PA 和 Lf),并改善肌肉减少症老年人的身体机能。